Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms

Curr Opin Neurol. 2002 Oct;15(5):525-31. doi: 10.1097/00019052-200210000-00002.


Purpose of review: Sporadic inclusion-body myositis (s-IBM) and hereditary inclusion body myopathies are progressive muscle diseases that lead to severe disability. We discuss recent advances in illuminating their pathogenic mechanism(s).

Recent findings: We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. Our basic hypothesis is that over-expression of amyloid-beta precursor protein within aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis: (a) increased transcription and accumulation of amyloid-beta precursor protein, and accumulation of its proteolytic fragment Abeta; (b) accumulations of phosphorylated tau and other Alzheimer-related proteins; (c) accumulation of cholesterol and low-density lipoprotein receptors, the cholesterol accumulation possibly due to its abnormal trafficking; (d) oxidative stress; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss unfolded and/or misfolded proteins as a possible mechanism in formation of the inclusion bodies and their consequences. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease brain are discussed.

Summary: Unfolding knowledge of the various pathogenetic aspects of the s-IBMs and hereditary inclusion body myopathies may lead to new therapeutic avenues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging / genetics
  • Aging / pathology
  • Alzheimer Disease / etiology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / adverse effects
  • Amyloid beta-Protein Precursor / metabolism*
  • Cholesterol / adverse effects
  • Humans
  • Myositis, Inclusion Body / etiology*
  • Myositis, Inclusion Body / genetics
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / physiopathology*
  • Oxidative Stress
  • Phenotype
  • Protein Folding
  • Receptors, Lipoprotein / metabolism
  • Up-Regulation
  • tau Proteins / adverse effects


  • Amyloid beta-Protein Precursor
  • Receptors, Lipoprotein
  • tau Proteins
  • Cholesterol